1. Field of the Invention
This invention relates to recombinant virus strains, live viral vaccines, methods of making the strains and vaccines, and methods of immunizing a host against viruses. More specifically, this invention relates to recombinant herpesvirus strains, live viral vaccines incorporating such strains, methods of making the recombinant strains and vaccines, and methods of immunizing a human host against herpes simplex virus types I and II (designated HSV-1 and HSV-2, respectively) using the vaccines.
2. Description of Related Art
Both distinguishable serotypes of herpes simplex virus (HSV-1 and HSV-2) cause infection and disease ranging from relatively minor fever blisters on lips to severe genital infections and generalized infections of newborns. Herpes simplex has increasingly been recognized as an etiologic agent in human encephalitis.
A stable, nontransforming live viral vaccine, which may or may not establish latent infections, and which is effective against both types of herpes simplex virus has long been sought.
In principle, viruses cause infected cells to produce specific proteins. These interact with each other and with cellular proteins, DNA or RNA to cause viral progeny to be made, to destroy the infected cell and to spread infection to previously noninfected cells. Some of these proteins also stimulate host immune response. HSV-1 and HSV-2 are related immunologically, but most of their proteins carry distinguishing characteristics which allow them to be differentiated. See Morse, et al., "Anatomy of Herpes Simplex Virus (HSV) DNA:X. Mapping of Viral Genes by Analysis of Polypeptides and Functions Specified by HSV-1.times.HSV-2 Recombinants", J. Virol., Vol. 26, No. 2 at 389-410 (May 1978), the disclosure of which is incorporated herein by reference.
It is known from the formation of recombinant progeny that proteins of HSV-1 can interact with proteins of HSV-2 to form infectious progeny. It is also known that immunity to HSV infection is determined by host response to several proteins.
A virus strain useful in a vaccine against HSV-1 and HSV-2 should be avirulent, stable (i.e. does not revert to the virulent state), provide demonstrated immunity to massive challenges of wild type strains of both HSV-1 and HSV-2, have low pathogenicity, and should not be capable of transforming host cells. In some cases, it may be desirable for the vaccinal virus to disappear after immunization of a host, but in some cases it may be desirable for the virus to remain in a latent form in the host.
Until now, no effective vaccine against both types of herpes simplex viruses exhibiting the desirable characteristics noted above has been known.